Drug use exerts tissue consequences and may be predisposed by specific alterations likely to be best detected in vivo using imaging approaches that seek individual differences predisposing to or consequent of drug abuse. In this FY, we have applied advanced statistical analyses to myocardial SPECT perfusion data to document patchy microvascular myocardial perfusion defects in research volunteers with histories of chronic cocaine self-administration, in comparison to data from age matchedvolunteers without histories of substance abuse. We are completing collaborative studies of 18F-deoxyglocose metabolic brain changes that correlate with the extent of cocaine craving experienced with chrronic cocaine users and controls are exposed to cocaine- associated stimuli. We are beginning studies that seek correlates between polymorphic gene markers at different neurtransmitter receptors and receptor densities measured in vivo using single-photon and positron- imaging techniques.